• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4937-4944
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• 2015

MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-99a has been reported as a tumor suppressor gene in various human cancers, but its functions in the context of anaplastic thyroid cancer (ATC) remain unknown. In this study, we reported that miR-99a was commonly downregulated in ATC tissue specimens and cell lines with important functional consequences. Overexpression of miR-99a not only dramatically reduced ATC cell viability by inducing cell apoptosis and accumulation of cells at G1 phase, but also inhibited tumorigenicity in vivo. We then screened and identified a novel miR-99a target, mammalian target of rapamycin (mTOR), and it was further confirmed by luciferase assay. Up-regulation of miR-99a would markedly reduce the expression of mTOR and its downstream phosphorylated proteins (p-4E-BP1 and p-S6K1). Similar to restoring miR-99a expression, mTOR down-regulation suppressed cell viability and increased cell apoptosis, whereas restoration of mTOR expression significantly reversed the miR-99a antitumor activity and the inhibition of mTOR/p-4E-BP1/p-S6K1 signal pathway profile. In clinical specimens and cell lines, mTOR was commonly overexpressed and its protein levels were statistically inversely correlated with miR-99a expression. Taken together, our results demonstrated for the first time that miR-99a functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting the mTOR/p-4E-BP1/p-S6K1 pathway in ATC cells. Given these, miR-99a may serve as a novel prognostic/diagnostic and therapeutic target for treating ATC.

• The Journal of Internal Korean Medicine
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• v.35 no.4
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• pp.416-427
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• 2014

Objectives: The purpose of this study was to investigate the antineoplastic effect of several herbal medicine mixtures (compositions of Astragalus membranaceu, Angelica gigas, Trichosanthes kirilowii, Panax ginseng, Rhus verniciflua Stokes) on the SNU-80 anaplastic thyroid carcinoma cell line. Methods: MTT assay was used to examine whether our herbal medicine mixtures decreased cell growth rate of SNU-80. Wound healing assay and Transwell invasion assay was performed to investigate whether our herbal medicine mixtures affect the migration and invasion of anaplastic cancer cells, SNU-80. ELISA assay was performed to know if our herbal medicine mixtures suppressed the expression of pro-invasive molecules, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) secreted from SNU-80. Results: MTT assay demonstrated that A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas :T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 strongly suppressed the growth of SNU-80. Wound healing assay demonstrated that A. membranaceus:A. gigas=3:1, A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 inhibited the migration of SNU-80. Transwell invasion assay demonstrated that A. membranaceus:A. gigas=1:1, A. membranaceus:A. gigas:T. kirilowii =1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng=1:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng :R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 inhibited the invasion of SNU-80. ELISA assay demonstrated that A. membranaceus :A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 suppressed the expression of VEGF. Also, A. membranaceus:A. gigas=1:1, A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus :A. gigas:T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes =1:1:1:1:1 or 3:1:1:1:1 suppressed the expression of MMP-2. Conclusions: The results obtained in this study suggest that several herbal medicine mixtures suppresse the growth and inhibit the migration and invasion of SNU-80, which is anaplastic thyroid cancer cells. Especially, A. membranaceus:A. gigas: T. kirilowii=1:1:1 mixture had a stronger anti-cancer effect.

• Journal of Society of Preventive Korean Medicine
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• v.18 no.1
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• pp.83-92
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• 2014

Objective : This study was performed to investigate the antineoplastic effect of Astragalus membranaceus, Angelica gigas, Rhus verniciflua Stokes and Trichosanthes kirilowii on SNU-80 anaplastic thyroid carcinoma cell line. Method : We examined whether our herbal medicines decreases cell growth rate of SNU-80 using MTT assay. We performed western blot analysis to verify that our herbal medicines induces apoptosis via caspase-dependent mechanism. We also performed wound healing assay and transwell invasion assay to investigate whether our herbal medicines affects the migration and invasion of anaplastic cancer cells, SNU-80. We also carried out ELISA assay to know our herbal medicines suppresses the expression of proinvasive molecules, such as VEGF and MMP-2 secreted from SNU-80. Results : MTT assay demonstrates that Angelica gigas, Rhus verniciflua Stokes, and Trichosanthes kirilowii suppressed strongly the growth of SNU-80. Western blot analysis demonstrates that Trichosanthes kirilowii induces apoptosis activating the cleavages of caspases (caspase-8, caspase-3) and PARP. Wound healing assay demonstrates that Rhus verniciflua Stokes, and Trichosanthes kirilowii inhibited the migration of SNU-80. Transwell invasion assay demonstrates that Rhus verniciflua Stokes, and Trichosanthes kirilowii inhibited the invasion of SNU-80. Elisa assay demonstrates that Astragalus membranaceus, Angelica gigas, Rhus verniciflua Stokes, and Trichosanthes kirilowii suppressed the expression of VEGF and MMP-2. Conclusion : We could conclude that several herbal medicines suppresses the growth and inhibits the migration and invasion of SNU-80 which is anaplastic thyroid cancer cells. Especially, Rhus verniciflua Stokes, Trichosanthes kirilowii had stronger anti-cancer effect suggesting that we can apply them to treat anaplastic thyroid cancer.

• 대한두경부종양학회:학술대회논문집
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• 2008.11a
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• pp.268-268
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• 2008

• The Korean Journal of Cytopathology
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• v.17 no.2
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• pp.126-135
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• 2006

To study the differentiating cytomorphological features of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) using fine needle aspiration cytology (FNAC), cytomorphological features of 16 patients with HL (n=8) or ALCL (n=8) were analyzed. In the initial cytological diagnosis prior to biopsy, HLs were properly diagnosed in 4 out of 8 cases (4 HL, 2 atypical, 2 benign), whereas all ALCL were diagnosed as malignancies. However, correct diagnosis of non-Hodgkin lymphoma (NHL) was made in only two ALCL patients (2 NHL, 1 HL, 1 sarcoma, 4 malignancy without specific type). Overall, the percentage of large abnormal cells ranged from 30% to 90% in ALCL except for one case, whereas it was less than 5% in all 8 HL. A spectrum of atypical cells was more characteristic of ALCL. In contrast, HL showed an sharp difference between reactive lymphoid cells and neoplastic ones (bimorphic pattern). Moreover, the emergence of kidney-shaped abnormal cells or wreath-like multinucleated cells was helpful in diagnosing ALCL. The combination of thesefeatures would be useful in differentiating HL and ALCL. Nevertheless, these two types of lymphomas cannot be definitely distinguished based on cytomorphological features alone. Therefore, the aim of FNAC would be to suggest a specific diagnosis and indicate the need for a biopsy.

• Journal of Microbiology and Biotechnology
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• v.32 no.3
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• pp.365-377
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• 2022

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.103-113
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• 2018

Purpose: Anaplastic thyroid cancer (ATC) is a rare tumor with a lethal clinical course despite aggressive multimodal therapy. Intensity-modulated radiotherapy (IMRT) may achieve a good therapeutic outcome in ATC patients, and the role of IMRT should be assessed. We retrospectively reviewed outcomes for ATC treated with three-dimensional conformal radiotherapy (3D-CRT) or IMRT to determine the optimal treatment option and explore the role of radiotherapy (RT). Materials and Methods: Between December 2000 and December 2015, 41 patients with pathologically proven ATC received RT with a sufficient dose of ${\geq}40Gy$. Among them, 21 patients (51%) underwent surgery before RT. Twenty-eight patients received IMRT, and 13 received 3D-CRT. Overall survival (OS) and progression-free survival (PFS), patterns of failure, and toxicity were examined. Results: The median follow-up time for survivors was 38.0 months. The median and 1-year OS and PFS rates were 7.2 months and 29%, 4.5 months and 15%, respectively. Surgery significantly improved the prognosis (median OS: 10.7 vs. 3.9 months, p = 0.001; median PFS: 5.9 vs. 2.5 months, p = 0.007). IMRT showed significantly better PFS and OS than 3D-CRT, even in multivariate analysis (OS: hazard ratio [HR] = 0.30, p = 0.005; PFS: HR = 0.33, p = 0.005). Significantly higher radiation dose could be delivered with IMRT than 3D-CRT ($EQD2_{10}$ 66 vs. 60 Gy, p = 0.005). Only 2 patients had grade III dermatitis after IMRT. No other severe toxicity ${\geq}grade$ III occurred. Conclusion: Patients with ATC showed better prognosis through multimodal treatment. Furthermore, IMRT could achieve favorable survival rates by safely delivering higher dose than 3D-CRT.

• Tuberculosis and Respiratory Diseases
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• v.78 no.4
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• pp.390-395
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• 2015

Primary anaplastic large cell lymphoma (ALCL) of the lung is highly aggressive and quite rare. We report here a case of anaplastic lymphoma kinase-positive endobronchial ALCL, that was initially thought to be primary lung cancer. A 68-year-old woman presented with hemoptysis, dyspnea, and upper respiratory symptoms persisting since 1 month. The hemoptysis and and bronchial obstruction lead to respiratory failure, prompting emergency radiotherapy and steroid treatment based on the probable diagnosis of lung cancer, although a biopsy did not confirm malignancy. Following treatment, her symptoms resolved completely. Chest computed tomography scan performed 8 months later showed increased and enlarged intra-abdominal lymph nodes, suggesting lymphoma. At that time, a lymph node biopsy was recommended, but the patient refused and was lost to follow up. Sixteen months later, the patient revisited the emergency department, complaining of persistent abdominal pain since several months. A laparoscopic intra-abdominal lymph node biopsy confirmed a diagnosis of ALCL.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7261-7264
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• 2013

Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome. These mutations have become molecular markers of significant diagnostic and prognostic relevance in the assessment of human gliomas. In the current study we evaluated IDH1 (R132) and IDH2 (R172) in 32 gliomas of various grades and tumor subtypes. Sequencing analysis revealed R132H mutations in 18.7% tumors, while none of the cases showed IDH2 (R172) mutations. The frequency of IDH1 mutations was higher in females (21.4%) than males (11.1%), and it was significantly higher in younger patients. Histological analyses demonstrated presence of necrosis and micro vascular proliferation in 69% and 75% respectively. Interestingly, IDH1 mutations were predominantly present in non-necrotic tumors as well as in cases showing microvascular proliferation. Of the six IDH1 positive cases, three were glioblastomas (IV), and one each were anaplastic oligoastrocytoma (III), anaplastic oligodendroglioma III (n=1) and diffuse astrocytoma. In conclusion, IDH1 mutations are quite frequent in Indian glioma patients while IDH2 mutations are not observed. Since IDH mutations are associated with good prognosis, their use in routine clinical practice will enable better risk stratification and management of glioma patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6315-6319
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• 2014

Background: Immunohistochemical markers are considered as important factors in diagnosis of malignant astrocytomas. The aim of the current study was to investigate the frequency of the immunohistochemical markers neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP) in malignant astrocytoma tumors in Firoozgar and Rasool-Akram hospitals from 2005 to 2010. Materials and Methods: In this cross-sectional study, immunohistochemical analysis of NFP and GFAP was performed on 79 tissue samples of patients with the diagnosis of anaplastic and glioblastoma multiform (GBM) astrocytomas. Results: The obtained results demonstrated that all patients were positive for GFAP and only 3.8% were positive for NFP. There was no significant association between these markers and clinical, demographic, and prognostic features of patients (p>0.05). Conclusions: NFP was expressed only in GBMs and not in anaplastic astrocytomas. It would be crucial to confirm the present findings in a larger number of tumors, especially in high grade gliomas.